To examine the early immunological events following helminth infection an in vitro model has been developed to prime CD4+CD45RA+ (naive) T cells obtained from unsensitized donors with microfilarial antigen using B-cells/monocytes as antigen presenting cells. This microfilarial Ag in the presence of IL-4 induces a strong IL-5 (Type-2) response whereas in its absence a Th0 (both IL-5 and IFN-gamma) occurs. This model has been extended to examine the role of antigen dose on the differentiation of naive T cells and the role of the important costimulatory molecues on skewing the immune response toward a Th2-dominated response. Further using human dendritic cells we have also been able to demonstate that parasite antigen profoundly alters the maturation and function of these cells. Because chronic filarial infections may alter immune reactivity to other (nonparasite) antigens and because these alterations may have profound implications for vaccine programs worldwide studies have shown that thepresence of active onchocerciasis blunts significantly the proliferative response along with IFN-gamma production to tetanus toxoid and changes the isotype profile of the antibody responses postvaccination to hepatitis B and to tetanus. A second, more comprehensive study, in which oral cholera vaccine was administered to patients with heavy intestinal helminth infection, has demonstrated even more dramatically that the immune response induced by these parasites alters not only the immune response to the orally administered vaccine, but also the 'take' of the vaccine. Because systemic helminth infection (e.g., filarial infections) can alter the cytokine milieu of the surrounding cells, its effect on HIV entry and replication was performed using an in vitro model. Acute helminth infection was very clearly associated with increased in vitro HIV replication compared to normal controls. Moreover, following definitive treatment with antiparasitic drugs, the increased replication seen in vitro returned to the normal levels.